8723 RESULTS
COMMENT Reducing amyloid two decades before symptoms does not guarantee that the intervention begins before pathology. An unanswered question is whether there would be success if those people at risk had an anti-amyloid drug on board so early that amyloid ...
COMMENT Another disappointing but not unexpected result. The hope is that we can learn a lot about the clinical trial design with regard to “confounding” parameters. A major underestimated problem is the effect size of the pharmacodynamic interactions between β ...
COMMENT Human BACE2 is an aspartyl protease, encoded by the BACE2 gene on chromosome 21 (Acquati et al., 2000; Bennett et al., 2000; Lin et al., 2000). BACE2 is homologous to BACE1 (the β-secretase). These two proteins are 45 percent identical in amino acid ...
COMMENT This paper is a technical tour de force and elegantly demonstrates the relevance of BACE2 as an anti-amyloidogenic protease, at least in trisomy 21 cerebral organoids. It also opens the exciting possibility that SNPs in BACE2 may control the age of onset ...
COMMENT These two papers from Fitzpatrick/Petrucelli and Scheres/Goedert represent a major advance toward a holistic structural understanding of the tau fibril conformers that drive distinct neurodegenerative tauopathies (i.e. "strains", which link ...
COMMENT Further evidence of the critical role of the cellular prion protein in neurodegenerative disorders. This evidence, showing PrPc acting as a receptor for other misfolded proteins, reveals a direct link between these misfolded proteins and synaptic ...
COMMENT This paper by Corbett et al. is an interesting piece of science related to the possible key role played by cellular prion protein (PrPc) in the neurotoxicity exerted by oligomeric forms of amyloid-β, α-synuclein, and tau, which have pathogenic roles in ...
COMMENT I was disappointed but also not completely surprised. Reasons include the small sample, the late increase in dose, and the unknown test characteristics of the four cognitive tests in this population, especially since some of the participants did not have ...
COMMENT Naturally it is disappointing that neither drug was found to slow cognitive decline. The trial was long in comparison to others—at least four years and up to seven for some participants. It represents a huge commitment on the part of participants and ...
COMMENT These two papers support each other, and, coming from two different teams and using different approaches, that is clearly a great strength. When it comes to neuropathology and genetic risk, the lines between AD, DLB, and PD (especially PDD) are becoming ...
COMMENT Genetic studies have shown that the APOE ε4 allele not only markedly increases risk for Alzheimer’s disease but also strongly associates with risk for developing Lewy body dementia (LBD). The exact role of APOE in LBD, however, is poorly understood. One ...
COMMENT I share the disappointment. Although the headline result is sadly negative, what has been shown for the first time is that it is possible to run a trial like this in familial AD. New ground has been broken in terms of showing that affected and at-risk ...
COMMENT I am disappointed, but not surprised. The trial sizes were very small, and cognitive readouts are notoriously relatively insensitive. The baseline intake was very heterogeneous in terms of cognitive status (CDR ranging from 0 to 1) and the escalation of ...
COMMENT DIAN-TU is a visionary study comprising valiant volunteers. The negative primary outcome is disappointing. Additional analyses are underway to learn as much as we can about Alzheimer’s disease from this trial. A platform has been created and is moving ...
COMMENT The initial negative results from the DIAN-TU trial regarding gantenerumab and solanezumab are terribly disappointing for the families and investigators who have committed so much time and effort to the trial over the past five years. We now need to go ...
